Dexter Y.L. Leung

Genome-wide association analyses identify multiple loci associated with central corneal thickness and keratoconus

Central corneal thickness (CCT) is associated with eye conditions including keratoconus and glaucoma. We performed a meta-analysis on >20,000 individuals in European and Asian populations that identified 16 new loci associated with CCT at genome-wide significance (P < 5 × 10−8). We further showed that 2 CCT-associated loci, FOXO1 and FNDC3B, conferred relatively large risks for keratoconus in 2 cohorts with 874 cases and 6,085 controls (rs2721051 near FOXO1 had odds ratio (OR) = 1.62, 95% confidence interval (CI) = 1.4–1.88, P = 2.7 × 10−10, and rs4894535 in FNDC3B had OR = 1.47, 95% CI = 1.29–1.68, P = 4.9 × 10−9). FNDC3B was also associated with primary open-angle glaucoma (P = 5.6 × 10−4; tested in 3 cohorts with 2,979 cases and 7,399 controls). Further analyses implicate the collagen and extracellular matrix pathways in the regulation of CCT.

Phacoemulsification versus combined phacotrabeculectomy in medically uncontrolled chronic angle closure glaucoma with cataracts.

OBJECTIVE To compare phacoemulsification alone versus combined phacotrabeculectomy in medically uncontrolled chronic angle closure glaucoma (CACG) with coexisting cataract. DESIGN Prospective randomized clinical trial. PARTICIPANTS Fifty-one medically uncontrolled CACG eyes with coexisting cataract of 51 patients. INTERVENTION Recruited patients were randomized into group 1 (phacoemulsification alone) or group 2 (combined phacotrabeculectomy with adjunctive mitomycin C). Postoperatively, patients were reviewed every 3 months for 2 years. MAIN OUTCOME MEASURES Intraocular pressure (IOP) and requirement for topical glaucoma drugs. RESULTS Twenty-seven CACG eyes were randomized into group 1, and 24 CACG eyes were randomized into group 2. Combined phacotrabeculectomy resulted in lower mean postoperative IOP than phacoemulsification alone at 3 months (14.0 vs. 17.0 mmHg, P = 0.01), 15 months (13.2 vs. 15.4 mmHg, P = 0.02), and 18 months (13.6 vs. 15.9 mmHg, P = 0.01). Combined phacotrabeculectomy resulted in 1.25 fewer topical glaucoma drugs (P<0.001) in the 24-month postoperative period, compared with phacoemulsification alone. Combined surgery was associated with more postoperative complications (P<0.001) and more progression of optic neuropathy (P = 0.03), compared with phacoemulsification alone. CONCLUSIONS Combined phacotrabeculectomy with adjunctive mitomycin C is more effective than phacoemulsification alone in controlling IOP in medically uncontrolled CACG eyes with coexisting cataract. Combined phacotrabeculectomy is associated with more postoperative complications.

Randomized Trial of Early Phacoemulsification versus Peripheral Iridotomy to Prevent Intraocular Pressure Rise after Acute Primary Angle Closure

PURPOSE To compare the efficacy of early phacoemulsification versus laser peripheral iridotomy (LPI) in the prevention of intraocular pressure (IOP) rise in patients after acute primary angle closure (APAC). DESIGN Prospective randomized controlled trial. PARTICIPANTS Sixty-two eyes of 62 Chinese subjects, with 31 eyes in each arm. METHODS Subjects were randomized to receive either early phacoemulsification or LPI after aborting APAC by medications. Patients were followed up on day 1; week 1; and months 1, 3, 6, 12, and 18. Predictors for IOP rise were studied. MAIN OUTCOME MEASURES Prevalence of IOP rise above 21 mmHg (primary) and number of glaucoma medications, IOP, and Shaffer gonioscopy grading (secondary). RESULTS Prevalences of IOP rise for the LPI group were 16.1%, 32.3%, 41.9%, and 46.7% for the follow-ups at 3, 6, 12, and 18 months, respectively. There was only one eye (3.2%) in the phacoemulsification group that had IOP rise at all follow-up time points (P<0.0001). Treatment by LPI was associated with significantly increased hazard of IOP rise (hazard ratio [HR], 14.9; 95% confidence interval [CI], 1.9-114.2; P = 0.009). In addition, a maximum IOP at presentation > 55 mmHg was associated with IOP rise (HR, 4.1; 95% CI, 1.3-13.0; P = 0.017). At 18 months, the mean number of medications required to maintain IOP <or= 21 mmHg was significantly higher in the LPI group (0.90+/-1.14) than in the phacoemulsification group (0.03+/-0.18, P<0.0001). Mean IOP for phacoemulsification group (12.6+/-1.9 mmHg) was consistently lower than that of the LPI group (15.0+/-3.4 mmHg, P = 0.009). Mean Shaffer grading for the phacoemulsification group (2.10+/-0.76) was consistently greater than that of the LPI group (0.73+/-0.64, P<0.0001). CONCLUSION Early phacoemulsification appeared to be more effective in preventing IOP rise than LPI in patients after abortion of APAC. High presenting IOP of >55 mmHg is an added risk factor for subsequent IOP rise. For patients with coexisting cataract and presenting IOP of >55 mmHg, early phacoemulsification can be considered as a definitive treatment to prevent IOP rise.

Phacoemulsification versus Trabeculectomy in Medically Uncontrolled Chronic Angle-Closure Glaucoma without Cataract

OBJECTIVE To compare phacoemulsification versus trabeculectomy with adjunctive mitomycin C in medically uncontrolled chronic angle-closure glaucoma (CACG) without cataract. DESIGN Prospective, randomized clinical trial. PARTICIPANTS Fifty medically uncontrolled CACG eyes without cataract of 50 patients. INTERVENTION Patients were randomized into undergoing either phacoemulsification or trabeculectomy with adjunctive mitomycin C. After surgery, patients were followed up every 3 months for 2 years. MAIN OUTCOME MEASURES Intraocular pressure (IOP) and requirement for glaucoma drugs. RESULTS Twenty-six CACG eyes were randomized to receive phacoemulsification, and 24 eyes underwent trabeculectomy with mitomycin C. Phacoemulsification and trabeculectomy resulted in significant and comparable IOP reduction at 24 months after surgery (reduction of 8.4 mmHg or 34% for phacoemulsification vs. 8.9 mmHg or 36% for trabeculectomy; P=0.76). Over first 24 months, trabeculectomy-treated eyes required on average 1.1 fewer drugs than phacoemulsification-treated eyes (P<0.001). However, trabeculectomy was associated with significantly more surgical complications than phacoemulsification (46% vs. 4%; P=0.001). Eight (33%) of 24 trabeculectomy eyes demonstrated cataract during follow-up. CONCLUSIONS Both phacoemulsification and trabeculectomy are effective in reducing IOP in medically uncontrolled CACG eyes without cataract. Trabeculectomy is more effective than phacoemulsification in reducing dependence on glaucoma drugs, but is associated with more complications. FINANCIAL DISCLOSURE(S) The author(s) have no proprietary or commercial interest in any materials discussed in this article.

Comparison between central corneal thickness measurements by ultrasound pachymetry and optical coherence tomography

Purpose:  Measurement of central corneal thickness (CCT) plays an important role in both diagnostic and therapeutic assessment of ocular diseases. Although ultrasound pachymetry (U‐PACH) is regarded as the golden standard for measurement of CCT, optical coherence tomography (OCT) may offer advantages as it can locate the central cornea with precision with no corneal touch. Nevertheless, the agreement of OCT with U‐PACH has not yet been gauged by Bland–Altman analysis. This study compares CCT measurement by OCT with that by U‐PACH.

Simvastatin and disease stabilization in normal tension glaucoma: a cohort study.

PURPOSE To investigate whether simvastatin use is associated with visual field (VF) stabilization in patients with normal tension glaucoma (NTG). DESIGN Prospective cohort study (ClinicalTrials.gov Identifier: NCT00321386). PARTICIPANTS A total of 256 eyes from 256 Chinese subjects with NTG. METHODS Patients were followed up at 4-month intervals for 36 months for VF progression per Andersons criteria. Clinical parameters were checked for association with progression in multivariate analysis. MAIN OUTCOME MEASURES The primary outcome was the association between simvastatin use and VF progression. RESULTS Thirty-one patients (12.1%) were taking simvastatin (statin+), and 225 patients (87.9%) were not taking simvastatin (statin-). Baseline age, gender, untreated intraocular pressure, VF indices, vertical cup-to-disc ratio, and central corneal thickness (CCT) were comparable between the 2 groups. There were significantly more patients with a history of hypercholesterolemia, systemic hypertension, and ischemic heart disease in the statin+ group. A total of 121 patients (47.3%) showed evidence of VF progression (mean rate of mean deviation loss was -0.30 decibel per year) during the 36 months of follow-up. Simvastatin use was among 8 of 121 patients (6.6%) who progressed compared with 23 of 135 patients (17.0%) who did not progress (P = 0.011). Logistic regression revealed that history of disc hemorrhage (relative risk [RR] 3.26; 95% confidence interval [CI], 1.21-8.76; P = 0.019), history of cerebrovascular accidents (RR 2.28; 95% CI, 1.03-5.06; P = 0.043), and baseline age (per 10 years older; RR 1.38; 95% CI, 1.08-1.76; P = 0.009) were significant risk factors for VF progression, whereas simvastatin use conferred a protective effect (RR 0.36; 95% CI, 0.14-0.91; P = 0.030). CONCLUSIONS Simvastatin use may be associated with VF stabilization in patients with NTG. A larger scale randomized controlled trial and cost-effectiveness analyses seem warranted.

Silent Cerebral Infarct and Visual Field Progression in Newly Diagnosed Normal-Tension Glaucoma: A Cohort Study

PURPOSE To investigate whether the presence of silent cerebral infarct (SCI) is related to field progression in patients with newly diagnosed normal-tension glaucoma (NTG). DESIGN Prospective cohort study. PARTICIPANTS A total of 286 eyes from 286 NTG patients: 64 with SCI (SCI+) and 222 without SCI (SCI-). METHODS Patients were assigned to the SCI+ or SCI- group depending on the presence of SCI as detected by cranial computed tomography scan at baseline. Patients were followed-up at 4-month intervals for 36 months for visual field progression as per Andersons criteria. MAIN OUTCOME MEASURES The primary outcome was the association between SCI and field progression. Secondary outcomes include the prevalence of SCI in NTG patients and other risk factors associated with progression. RESULTS There were no significant differences in the baseline intraocular pressures (IOPs), fluctuation amplitude of pretreatment IOP, baseline visual acuity, vertical cup-to-disc ratio, vertical disc diameter, presenting field indices, and central corneal thickness (CCT) between the 2 groups. Patients with SCI were significantly older compared with SCI- patients (72.4+/-10.7 vs. 63.2+/-14.2 years; P<0.001). Univariate analyses revealed age, fluctuation amplitude of pretreatment IOP, thinner CCT, presence of disc hemorrhage, systemic hypertension, arrhythmia, and SCI were significant for field progression. Silent cerebral infarct was present in 29.6% of field-progressed subjects versus 15.3% of field-stable subjects (P = 0.004). Kaplan-Meier survival analysis revealed that 65.6% of SCI+ versus 45.9% of SCI- patients had progressed (P = 0.003). Cox proportional hazards regression analysis showed disc hemorrhage (hazard ratio [HR], 2.28; 95% confidence interval [CI], 1.54-3.37; P<0.001), SCI (HR, 1.61; 95% CI, 1.09-2.36; P = 0.016), systemic hypertension (HR, 1.48; 95% CI, 1.04-2.10; P = 0.029), and CCT (per 30 mum of thinning; HR, 1.35; 95% CI, 1.16-1.75; P<0.001) were associated with field progression. Other variables significant in the univariate analysis were not significant in the regression model. The most common location of SCI was at the basal ganglia. CONCLUSIONS Presence of SCI may be an independent risk factor for visual field progression in patients with NTG.

Canaliculitis Associated with a Combined Infection of Lactococcus lactis cremoris and Eikenella corrodens

Bacteria of the genus Lactococcus are Gram-positive and generally are recognized as nonpathogenic to humans. To the best of our knowledge, this genus has not been reported in human ocular infections. Eikenella corrodens is a slowly growing, facultatively anaerobic and Gram-negative bacillus. A rare case of canaliculitis associated with Eikenella corrodens has been reported. Here we present an unusual case of canaliculitis associated with a mixed infection by both organisms.

Long-term results of oral valganciclovir for treatment of anterior segment inflammation secondary to cytomegalovirus infection

Background The purpose of this study was to assess the efficacy of oral valganciclovir in the treatment of anterior segment inflammation caused by cytomegalovirus (CMV) infection. Methods Consecutive patients with anterior segment inflammation due to CMV causing anterior uveitis or corneal endotheliitis treated with oral valganciclovir were reviewed. Diagnosis of CMV infection was confirmed by polymerase chain reaction of the aqueous aspirate prior to commencement of oral valganciclovir. All patients were treated with an oral loading dose of 900 mg valganciclovir twice daily for at least 2 weeks, followed by an additional 450 mg valganciclovir twice-daily maintenance therapy. Changes in visual acuity, intraocular pressure (IOP), use of antiglaucomatous eye drops, and recurrence were analyzed. Results Thirteen eyes of 11 patients were followed for a mean of 17.2 months. Two patients had bilateral corneal endotheliitis. All eyes had absence of anterior segment inflammation within 3 weeks after treatment. Following treatment, the mean logMAR visual acuity improved significantly from 0.58 at baseline to 0.37 at the last follow-up (P = 0.048). The mean IOP and number of antiglaucomatous eye drops also decreased significantly (P = 0.021 and P = 0.004, respectively). Five (38.5%) eyes had recurrence of anterior uveitis after valganciclovir was stopped and required retreatment with oral valganciclovir. Conclusion Oral valganciclovir appeared to be effective in controlling CMV anterior uveitis, resulting in visual improvement and IOP reduction following control of inflammation. However, despite the initial clinical response in all cases, recurrence after cessation of oral valganciclovir could occur.

Intraocular pressure measurement in patients with previous LASIK surgery using pressure phosphene tonometer.

Purpose: To compare intraocular pressure (IOP) assessment in post‐LASIK patients using non‐contact tonometry, pressure phosphene tonometry and applanation tonometry.